ABSTRACT Although inflammation is increasingly believed to be involved in prostate carcinogenesis, responsible cause(s) of inflammation are still unclear. One promising, possible responsible cause is Trichomonas vaginalis infection (trichomonosis), a common, sexually transmitted protozoan infection with known prostate involvement. We previously investigated trichomonosis and prostate cancer risk in three epidemiologic studies of predominantly White men, two of which observed a positive association between T. vaginalis serostatus and prostate cancer, particularly high-grade or late-stage disease, while the third observed no association with very early-stage disease. Collectively, these findings suggest that trichomonosis may be associated with risk of aggressive prostate cancer, at least in White men. To our knowledge, no studies have investigated associations between trichomonosis and prostate cancer risk among Black men, despite their higher risks of both trichomonosis and prostate cancer. Therefore, to extend our promising findings for trichomonosis and prostate cancer risk to Black men (Aim 1), and to investigate the relation between trichomonosis and aggressive prostate cancer risk (Aim 2), we propose to conduct an epidemiologic investigation of trichomonosis and prostate cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). The proposed study will be the largest investigation of trichomonosis and prostate cancer risk to date, and will build upon promising findings from a previous nested case-control study of sexually transmitted infections (STIs) and prostate cancer risk in PLCO, in which the authors observed no associations between individual STIs and risk of prostate cancer, but a modest positive association between a history of any STIs combined and prostate cancer, suggesting that another unmeasured STI, such as trichomonosis, might be associated with risk of prostate cancer in this study population. The proposed study is timely and innovative because it extends our recently observed promising findings for trichomonosis and prostate cancer risk among predominantly White men to Black men, and it is significant because our findings could lead to the development of novel primary prevention strategies for prostate cancer, particularly prostate cancer with the greatest potential for progression to fatal disease. Primary prevention strategies based on our findings would be simple and inexpensive to implement because trichomonosis can be easily prevented by safe sexual behavior, and easily screened and treated with currently available, inexpensive antibiotics. A vaccine could also conceivably be developed for this common infection. Therefore, given the potentially high public health and clinical impact of our findings, extension to important sub-groups of men (i.e., Black men), and confirmation of our suggestive findings for aggressive disease are clearly needed. PUBLIC HEALTH RELEVANCE: PROJECT NARRATIVE The proposed study is relevant to public health because it investigates a promising, possible cause (Trichomonas vaginalis infection or trichomonosis) of prostate cancer, particularly prostate cancer that is most likely to be fatal. Very little is currently known about the cause(s) of prostate cancer, and few prevention strategies exist. Therefore, if we observe a positive association between a history of trichomonosis and prostate cancer risk in our study, this finding could lead to a better understanding of prostate cancer development, and novel prevention strategies for prostate cancer, such as prevention of trichomonosis through reduced risky sexual behaviors or vaccine development, and screening and treatment of existing infections by antibiotics.